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repelling class discrimination: ephrin-a5 binds to and activates ephb2 receptor signaling.the interactions between eph receptor tyrosine kinases and their ephrin ligands regulate cell migration and axon pathfinding. the epha receptors are generally thought to become activated by ephrin-a ligands, whereas the ephb receptors interact with ephrin-b ligands. here we show that two of the most widely studied of these molecules, ephb2 and ephrin-a5, which have never been described to interact with each other, do in fact bind one another with high affinity. exposure of ephb2-expressing cells ...200415107857
changes of the secondary structure of the 5' end of the sindbis virus genome inhibit virus growth in mosquito cells and lead to accumulation of adaptive mutations.both the 5' end of the sindbis virus (sin) genome and its complement in the 3' end of the minus-strand rna synthesized during virus replication serve as parts of the promoters recognized by the enzymes that comprise the replication complex (rdrp). in addition to the 5' untranslated region (utr), which was shown to be critical for the initiation of replication, another 5' sequence element, the 51-nucleotide (nt) conserved sequence element (cse), was postulated to be important for virus replicatio ...200415113874
regional differences in viral growth and central nervous system injury correlate with apoptosis.infection of neonatal mice with reovirus t3 dearing (t3d), the prototypic neurotropic reovirus, causes fatal encephalitis associated with neuronal injury and virus-induced apoptosis throughout the brain. t3d variant k (vark) is an antigenic variant that has a nearly 1 million-fold reduction in neurovirulence following intracerebral (i.c.) inoculation compared to t3d and a restricted pattern of central nervous system injury with damage limited to the hippocampus, sparing other brain regions. we w ...200415113925
receptor-dependent coronavirus infection of dendritic cells.in several mammalian species, including humans, coronavirus infection can modulate the host immune response. we show a potential role of dendritic cells (dc) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the jaw sii dc line and primary dc from balb/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine ceacam1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway.200415113927
human immunodeficiency virus type 1 envelope glycoproteins that lack cytoplasmic domain cysteines: impact on association with membrane lipid rafts and incorporation onto budding virus particles.the human immunodeficiency virus type 1 (hiv-1) envelope comprises a surface gp120 and a transmembrane gp41. the cytoplasmic domain of gp41 contains cysteine residues (c764 and c837) which are targets for palmitoylation and were reported to be required for envelope association with lipid rafts and assembly on budding virions (i. rousso, m. b. mixon, b. k. chen, and p. s. kim, proc. natl. acad. sci. usa 97:13523-13525, 2000). several infectious hiv-1 clones contain envelopes that have no gp41 cyt ...200415113929
axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats.we generated spinal motoneurons from embryonic stem (es) cells to determine the developmental potential of these cells in vitro and their capacity to replace motoneurons in the adult mammalian spinal cord. es cell-derived motoneurons extended long axons, formed neuromuscular junctions, and induced muscle contraction when cocultured with myoblasts. we transplanted motoneuron-committed es cells into the spinal cords of adult rats with motoneuron injury and found that approximately 3,000 es cell-de ...200415118094
persistent infection and suppression of host response by alphaviruses.alphaviruses cause chronic noncytopathic infection in mosquito cells and develop a highly cytopathic infection in a wide variety of cells of vertebrate origin. upon infection, alphaviruses modify cellular processes to meet the virus needs for propagation. downregulation of translation and transcription caused by viral infection appears to reduce interferon (ifn) and cytokine gene expression and allows more efficient dissemination of infection. alphaviruses with mutations in nonstructural protein ...200415119769
photodynamic therapy: a new antimicrobial approach to infectious disease?photodynamic therapy (pdt) employs a non-toxic dye, termed a photosensitizer (ps), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. pdt has the advantage of dual selectivity, in that the ps can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. pdt has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or pati ...200415122361
poliovirus rna-dependent rna polymerase (3dpol): pre-steady-state kinetic analysis of ribonucleotide incorporation in the presence of mg2+.we have solved the complete kinetic mechanism for correct nucleotide incorporation catalyzed by the rna-dependent rna polymerase from poliovirus, 3d(pol). the phosphoryl-transfer step is flanked by two isomerization steps. the first conformational change may be related to reorientation of the triphosphate moiety of the bound nucleotide, and the second conformational change may be translocation of the enzyme into position for the next round of nucleotide incorporation. the observed rate constant ...200415122878
processing of a pestivirus protein by a cellular protease specific for light chain 3 of microtubule-associated proteins.the genome of the cytopathogenic (cp) bovine viral diarrhea virus (bvdv) jacp contains a cellular insertion coding for light chain 3 (lc3) of microtubule-associated proteins, the mammalian homologue of yeast aut7p/apg8p. the cellular insertion induces cp bvdv-specific processing of the viral polyprotein by a cellular cysteine protease homologous to the known yeast protease aut2p/apg4p. three candidate bovine protease genes were identified on the basis of the sequence similarity of their products ...200415140988
virus inactivation and protein recovery in a novel ultraviolet-c reactor.ultraviolet-c (uvc) irradiation is a viral-inactivation method that was dismissed by many plasma fractionators as a result of the potential for protein damage and the difficulty in delivering uniform doses. a reactor with novel spiral flow hydraulic mixing was recently designed for uniform and controlled uvc treatment. the objective of this study was to investigate virus inactivation and protein recovery after treatment through the new reactor.200415144527
independent functions of hsp90 in neurotransmitter release and in the continuous synaptic cycling of ampa receptors.the delivery of neurotransmitter receptors into synapses is essential for synaptic function and plasticity. in particular, ampa-type glutamate receptors (ampa receptors) reach excitatory synapses according to two distinct routes: a regulated pathway, which operates transiently during synaptic plasticity, and a constitutive pathway, which maintains synaptic function under conditions of basal transmission. however, the specific mechanisms that distinguish these two trafficking pathways are essenti ...200415152036
inhibition of reovirus by mycophenolic acid is associated with the m1 genome segment.mycophenolic acid (mpa), an inhibitor of imp dehydrogenase, inhibits reovirus replication and viral rna and protein production. in mouse l929 cells, antiviral effects were greatest at 30 microg of mpa/ml. at this dosage, mpa inhibited replication of reovirus strain t3d more than 1,000-fold and inhibited replication of reovirus strain t1l nearly 100-fold, compared to non-drug-treated controls. genetic reassortant analysis indicated the primary determinant of strain-specific differences in sensiti ...200415163710
mcp-1 and ccr2 contribute to non-lymphocyte-mediated brain disease induced by fr98 polytropic retrovirus infection in mice: role for astrocytes in retroviral neuropathogenesis.virus infection of the central nervous system (cns) often results in chemokine upregulation. although often associated with lymphocyte recruitment, increased chemokine expression is also associated with non-lymphocyte-mediated cns disease. in these instances, the effect of chemokine upregulation on neurological disease is unclear. in vitro, several chemokines including monocyte chemotactic protein 1 (mcp-1) protect neurons from apoptosis. therefore, in vivo, chemokine upregulation may be a prote ...200415163738
regulation of semliki forest virus rna replication: a model for the control of alphavirus pathogenesis in invertebrate hosts.alphavirus nonstructural proteins are translated as a polyprotein that is ultimately cleaved into four mature proteins called nsp1, nsp2, nsp3, and nsp4 from their order in the polyprotein. the role of this nonstructural polyprotein, of cleavage intermediates, and of mature proteins in synthesis of semliki forest virus (sfv) rna has been studied using mutants unable to cleave one or more of the sites in the nonstructural polyprotein or that had the arginine sense codon between nsp3 and nsp4 chan ...200415165827
neuronal apoptosis pathways in sindbis virus encephalitis.sindbis virus infects neurons of the brain and spinal cord leading to neuronal apoptosis and encephalitis in mice. during postnatal development, neurons of mice remain susceptible to infection but become refractory to sv-induced programmed cell death. failure to undergo programmed cell death results in a persistent infection. however, some neurovirulent strains of sindbis virus overcome the age-dependent protective function in neurons, leading to enhanced apoptotic cell death in the central nerv ...200415171608
identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions.sympathetic premotor neurons directly control sympathetic preganglionic neurons (spns) in the intermediolateral cell column (iml) of the thoracic spinal cord, and many of these premotor neurons are localized in the medulla oblongata. the rostral ventrolateral medulla contains premotor neurons controlling the cardiovascular conditions, whereas rostral medullary raphe regions are a candidate source of sympathetic premotor neurons for thermoregulatory functions. here, we show that these medullary r ...200415190110
regulation of synaptic strength and ampa receptor subunit composition by pick1.pick1 (protein interacting with c kinase-1) regulates the surface expression of the ampa receptor (ampar) glur2 subunit, however, the functional consequences of this interaction are not well understood. previous work has suggested that pick1 promotes the internalization of ampars. however, we found that when pick1 is virally expressed in the ca1 region of hippocampal slices, it causes an increase in ampar-mediated epsc amplitude. this effect is associated with increased ampar rectification and s ...200415190111
identification of the amino acid sequence in sindbis virus nsp4 that binds to the promoter for the synthesis of the subgenomic rna.a gel mobility-shift assay was used to demonstrate the binding of the sindbis virus transcriptase to the promoter for the synthesis of subgenomic (sg) rna. the assay made use of a p15 fraction (the cell fraction that is pelleted at 15,000 x g) from cells infected with recombinant vaccinia virions expressing various sindbis virus nonstructural proteins (nsps) and a (32)p-labeled 24-mer oligoribonucleotide representing the minimal sequence with sg promoter activity. by itself, nsp4, the viral rna- ...200415197279
endemic venezuelan equine encephalitis in northern peru.since venezuelan equine encephalitis virus (veev) was isolated in peru in 1942, >70 isolates have been obtained from mosquitoes, humans, and sylvatic mammals primarily in the amazon region. to investigate genetic relationships among the peru veev isolates and between the peru isolates and other veev strains, a fragment of the pe2 gene was amplified and analyzed by single-stranded conformation polymorphism. representatives of seven genotypes underwent sequencing and phylogenetic analysis. the res ...200415200823
causative agent of pogosta disease isolated from blood and skin lesions.pogosta disease is a mosquito-borne viral disease in finland, which is clinically manifested by rash and arthritis; larger outbreaks occur in 7-year intervals. the causative agent of the disease has been suspected of being closely related to sindbis virus (sinv). we isolated sinv from five patients with acute pogosta disease during an outbreak in fall 2002 in finland. one virus strain was recovered from a whole blood sample and four other strains from skin lesions. the etiology of pogosta diseas ...200415200824
yellow fever outbreak, imatong, southern sudan.in may 2003, the world health organization received reports about a possible outbreak of a hemorrhagic disease of unknown cause in the imatong mountains of southern sudan. laboratory investigations were conducted on 28 serum samples collected from patients in the imatong region. serum samples from 13 patients were positive for immunoglobulin m antibody to flavivirus, and serum samples from 5 patients were positive by reverse transcription-polymerase chain reaction with both the genus flavivirus- ...200415207058
conformational changes in sindbis virions resulting from exposure to low ph and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion.alphaviruses have the ability to induce cell-cell fusion after exposure to acid ph. this observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid ph after incorporation into a cell endosome. we have investigated the requirements for the induction of virus-mediated, low ph-induced cell-cell fusion and cell-virus fusion. we have correlated the ph requirements for this process to ...200415207623
doxorubicin and paclitaxel enhance the antitumor efficacy of vaccines directed against her 2/neu in a murine mammary carcinoma model.the purpose of the present study was to determine whether cytotoxic chemotherapeutic agents administered prior to immunotherapy with gene vaccines could augment the efficacy of the vaccines.200415217493
positive effect of the hepatitis c virus nonstructural 5a protein on viral multiplication.hepatitis c virus infection (hcv), is a major cause of liver disease worldwide, and are frequently resistant to the interferon alpha treatment. the nonstructural (ns) 5a protein of hcv has been proposed to be involved in this resistance. additional studies have pointed out a role for ns5a in several other cellular interactions as well as an important role of its adaptative mutations in hcv genome replication. however, no infectious system is available to assess the role of ns5a in the hcv life c ...200415221536
bad is a pro-survival factor prior to activation of its pro-apoptotic function.the mammalian bad protein belongs to the bh3-only subgroup of the bcl-2 family. in contrast to its known pro-apoptotic function, we found that endogenous and overexpressed bad(l) can inhibit cell death in neurons and other cell types. several mechanisms regulate the conversion of bad from an anti-death to a pro-death factor, including alternative splicing that produces the n-terminally truncated bad(s). in addition, caspases convert bad(l) into a pro-death fragment that resembles the short splic ...200415231831
input- and subunit-specific ampa receptor trafficking underlying long-term potentiation at hippocampal ca3 synapses.hippocampal ca3 pyramidal neurons receive synaptic inputs from both mossy fibres (mfs) and associational fibres (afs). long-term potentiation (ltp) at these synapses differs in its induction sites and n-methyl-d-aspartate receptor (nmdar) dependence. most evidence favours the presynaptic and postsynaptic mechanisms for induction of mf ltp and af ltp, respectively. this implies that molecular and functional properties differ between mf and af synapses at both presynaptic and postsynaptic sites. i ...200415245483
the pdz domain of pick1 differentially accepts protein kinase c-alpha and glur2 as interacting ligands.the c terminus (ct) of protein kinase c-alpha (pkcalpha) has a type i pdz binding motif, whereas glur2 has a type ii pdz binding motif. both motifs are recognized by the pdz domain of protein interacting with protein kinase c (pick1), and pick1-pkcalpha-controlled phosphorylation regulates the synaptic expression and function of glur2. here, we show that a specific mutation within the carboxylate-binding loop of the pdz domain of pick1 (k27e; pick1-ke) results in a loss of interaction with glur2 ...200415247289
cytokine-mediated downregulation of coxsackievirus-adenovirus receptor in endothelial cells.endothelial cells have the ability to change their complement of cell surface proteins in response to inflammatory cytokines. we hypothesized that the expression of the coxsackievirus-adenovirus receptor (car), a viral receptor and putative cell-cell adhesion molecule, may be altered during the response of endothelial cells to inflammation. to test this hypothesis, we evaluated car protein and mrna levels in human umbilical vein endothelial cells after they were exposed to tumor necrosis factor ...200415254176
role of cd8+ t cells in control of west nile virus infection.infection with west nile virus (wnv) causes fatal encephalitis more frequently in immunocompromised humans than in those with a healthy immune system. although a complete understanding of this increased risk remains unclear, experiments with mice have begun to define how different components of the adaptive and innate immune response function to limit infection. previously, we demonstrated that components of humoral immunity, particularly immunoglobulin m (igm) and igg, have critical roles in pr ...200415254203
inactivation of west nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma-derived products.human plasma is the source of a wide variety of therapeutic proteins, yet it is also a potential source of viral contamination. recent outbreaks of emergent viral pathogens, such as west nile virus, and the use of live vaccinia virus as a vaccine have prompted a reassessment of the viral safety of plasma-derived products. the purpose of this study was to evaluate the efficacy of current viral inactivation methods for west nile and vaccinia viruses and to reassess the use of model viruses to pred ...200415260817
venezuelan equine encephalitis emergence: enhanced vector infection from a single amino acid substitution in the envelope glycoprotein.in 1993 and 1996, subtype ie venezuelan equine encephalitis (vee) virus caused epizootics in the mexican states of chiapas and oaxaca. previously, only subtype iab and ic vee virus strains had been associated with major outbreaks of equine and human disease. the iab and ic epizootics are believed to emerge via adaptation of enzootic (sylvatic, equine-avirulent) strains for high titer equine viremia that results in efficient infection of mosquito vectors. however, experimental equine infections w ...200415277679
pkr-dependent and -independent mechanisms are involved in translational shutoff during sindbis virus infection.the replication of sindbis virus (sin) profoundly affects the metabolism of infected vertebrate cells. one of the main events during sin infection is the strong inhibition of translation of cellular mrnas. in this study, we used a combination of approaches, including the study of sin replication in pkr(-/-) mouse embryo fibroblasts or in the presence of an excess of catalytically inactive pkr. we show that the pkr-dependent inhibition of translation is not the only and most likely not the major ...200415280454
heparan sulfate-independent infection attenuates high-neurovirulence gdvii virus-induced encephalitis.the high-neurovirulence theiler's murine encephalomyelitis virus (tmev) strain gdvii uses heparan sulfate (hs) as a coreceptor to enter target cells. we report here that gdvii virus adapted to growth in hs-deficient cells exhibited two amino acid substitutions (r3126l and n1051s) in the capsid and no longer used hs as a coreceptor. infectious-virus yields in cho cells were 25-fold higher for the adapted virus than for the parental gdvii virus, and the neurovirulence of the adapted virus in intra ...200415280499
rapid preparative purification of west nile and sindbis virus pcr products utilizing a microbore anion-exchange column.analysis and purification of specific pcr products from pcr reactions can be problematic due to several issues relating to amplification and low product yield. the use of hplc as a preparative tool in pcr product analysis is common but has not replaced traditional electrophoretic techniques for purifying dna to be used in subsequent experiments. gel purification of pcr products can result in a net loss greater than 50% of the starting dna amount. thus, this method of recovery can become the limi ...200415288956
attenuation of dengue virus infection by adeno-associated virus-mediated sirna delivery.background: the need for safe and effective treatment of dengue virus (den), a class a agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. an effective vaccine for den is not yet available. in this study the possibility of attenuating den infection using adeno-associated virus (aav)-encoded short interfering rnas (sirna) was examined in vero cells and human dendritic cells (dcs). methods: a cassette encoding sirna targeted to a 3' untranslated s ...200415301687
subcellular localization and calcium and ph requirements for proteolytic processing of the hendra virus fusion protein.proteolytic cleavage of the hendra virus fusion (f) protein results in the formation of disulfide-linked f1 and f2 subunits, with cleavage occurring after residue k109 in the sequence gdvk/l. this unusual cleavage site and efficient propagation of hendra virus in a furin-deficient cell line indicate that the hendra f protein is not cleaved by furin, the protease responsible for proteolytic activation of many viral fusion proteins. to identify the subcellular site of hendra f processing, vero cel ...200415308711
phototoxicity against tumor cells and sindbis virus by an octahedral rhodium bisbipyridyl complex and evidence for the genome as a target in viral photoinactivation.an octahedral rhodium complex (cis-dichloro(dipyrido[3,2a-2',3'c]phenazine)(1,10-phenanthroline)rhodium(iii) chloride; dppzphen) has been prepared that can penetrate tumor cell membranes and the sindbis viral capsid. the compound is phototoxic to these entities when irradiated with uva light. model studies with calf thymus and supercoiled plasmid dna indicate that the complex can both bind with, and nick, nucleic acid. analysis of sindbis virus, following irradiation with the metal complex, conf ...200415310216
effects of ras and rap1 on electrical excitability of differentiated ng108-15 cells.effects of two small g-proteins, rap1 and ras, on the sodium channel activity in ng108-15 cells were studied using sindbis virus-mediated gene transfer. when an activated rap1a mutant (rap1-12v, the activated mutant of rap1 carrying glycine to valine substitution at codon 12) or a dominant-negative h-ras mutant (ras-17n, carrying serine to asparagine substitution at codon 17) was expressed in differentiated ng108-15 cells, the proportion of cells generating action potential decreased and the amp ...200415312909
viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicity.neuroadapted sindbis virus (nsv) is a neurotropic virus capable of inducing the death of spinal motor neurons in mice and rats. in this study we investigated the mechanisms that underlie nsv-induced motor neuron death. we found that many degenerating spinal motor neurons were not infected directly with nsv, suggesting that bystander cell death occurs. an excitotoxic mechanism was confirmed when blockade of calcium-permeable ampa receptors attenuated motor neuron death both in vitro and in vivo. ...200415329404
intranasal immunization with inactivated influenza virus enhances immune responses to coadministered simian-human immunodeficiency virus-like particle antigens.intranasal immunization with inactivated influenza virus vaccine can provide protective immunity, whereas many other antigens are less effective when used for mucosal immunization. to determine whether influenza virus could enhance immune responses to an antigen coadministered to a mucosal surface, we studied the intranasal immunization of mice with a mixture of simian-human immunodeficiency virus (shiv) virus-like particles (vlps) and inactivated influenza virus. compared to mice immunized with ...200415331695
a mutant of sindbis virus which is able to replicate in cells with reduced ctp makes a replicase/transcriptase with a decreased km for ctp.we reported earlier the isolation and characterization of a sindbis virus mutant, sv(pzf), that can grow in mosquito cells treated with pyrazofurin (pzf), a compound that interferes with pyrimidine biosynthesis (y. h. lin, p. yadav, r. ravatn, and v. stollar, virology 272:61-71, 2000; y. h. lin, h. a. simmonds, and v. stollar, virology 292:78-86, 2002). three amino acid changes in nsp4, the viral rna polymerase, were required to produce this phenotype. we now describe a mutant of sindbis virus, ...200415331697
discrimination among rhinovirus serotypes for a variant icam-1 receptor molecule.intercellular adhesion molecule 1 (icam-1) is the cellular receptor for the major group of human rhinovirus serotypes, including human rhinovirus 14 (hrv14) and hrv16. a naturally occurring variant of icam-1, icam-1kilifi, has altered binding characteristics with respect to different hrv serotypes. hrv14 binds to icam-1 only transiently at physiological temperatures but forms a stable complex with icam-1kilifi. conversely, hrv16 forms a stable complex with icam-1 but does not bind to icam-1kilif ...200415331736
the immunoglobulin family member dendrite arborization and synapse maturation 1 (dasm1) controls excitatory synapse maturation.in the developing mammalian brain, a large fraction of excitatory synapses initially contain only n-methyl-d-aspartate receptor and thus are "silent" at the resting membrane potential. as development progresses, synapses acquire alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (ampa-rs). although this maturation of excitatory synapses has been well characterized, the molecular basis for this developmental change is not known. here, we report that dendrite arborization and synap ...200415340156
biological diversity versus risk for mosquito nuisance and disease transmission in constructed wetlands in southern sweden.in southern sweden, many wetlands have been constructed, and maintaining or increasing biological diversity is often included in the aims. some wetlands are constructed near human settlements, thus raising the problem of wetlands being associated with mosquitoes (diptera: culicidae). increased biodiversity (including mosquito diversity) is considered desirable, whereas mosquito nuisance from a human point of view is not. adult mosquito abundance, diversity and species assemblages of constructed ...200415347393
sindbis viral-mediated expression of egfp-dopamine d1 receptors in situ with real-time two-photon microscopic detection.dopamine d1 receptors (d1drs) mediate a major component of dopaminergic neurotransmission, and alterations in their synaptic and subcellular distribution may underlie a variety of neurological diseases. in order to monitor d1dr localization in real time, we subcloned a sindbis virus containing an enhanced-gfp coding region inserted at the c-terminal region of a dopamine d1 receptor (egfp-d1dr). two-photon excitation of expressed egfp-d1drs was monitored in a variety of viable neural preparations ...200415351518
zap is a crm1-dependent nucleocytoplasmic shuttling protein.the zinc finger antiviral protein (zap) is a recently isolated host antiviral factor. it specifically inhibits the replication of moloney murine leukemia virus (mmlv) and sindbis virus (sin) by preventing the accumulation of viral rna in the cytoplasm. in this report, we demonstrate that zap is predominantly localized in the cytoplasm at steady state but shuttles between the nucleus and the cytoplasm in a crm1-dependent manner. two nuclear localization sequences (nls) and one nuclear export sequ ...200415358138
human immunodeficiency virus type 1 gag-specific mucosal immunity after oral immunization with papillomavirus pseudoviruses encoding gag.mucosal surfaces are the primary portals for human immunodeficiency virus (hiv) transmission. because systemic immunization, in general, does not induce effective mucosal immune responses, a mucosal hiv vaccine is urgently needed. for this study, we developed papillomavirus pseudoviruses that express hiv-1 gag. the pseudoviruses are synthetic, nonreplicating viruses, yet they can produce antigens for a long time in the immune system. here we show that oral immunization of mice by the use of papi ...200415367590
structural properties of a multifunctional t-shaped rna domain that mediate efficient tomato bushy stunt virus rna replication.in positive-strand rna viruses, 5' untranslated regions (5' utrs) mediate many essential viral processes, including genome replication. previously, we proposed that the 5'-terminal portion of the genomic leader sequence of tomato bushy stunt virus (tbsv) forms an rna structure containing a 3-helix junction, termed the t-shaped domain (tsd). in the present study, we have carried out structure-function analysis of the proposed tsd and have confirmed an important role for this domain in mediating e ...200415367615
temporal modulation of an autoprotease is crucial for replication and pathogenicity of an rna virus.pestiviruses belong to the family flaviviridae, and their genome is a single-stranded rna of positive polarity encoding one large polyprotein which is further processed into mature proteins. noncytopathogenic (noncp) strains of the pestivirus bovine viral diarrhea virus (bvdv) can establish persistent infection. in persistently infected animals, noncp bvdvs occasionally acquire mutations in viral nonstructural protein 2 (ns2) that give rise to cytopathogenic (cp) bvdv variants, and, eventually, ...200415367643
gene therapy for malignant glioma using sindbis vectors expressing a fusogenic membrane glycoprotein.malignant glioma has a dismal prognosis. it was previously shown that glioma cells are efficiently killed when they express a gene coding for a hyperfusogenic mutant of the gibbon ape leukemia virus envelope glycoprotein (galv.fus). however, production of viral vectors expressing galv.fus has proven problematic because the transgene is toxic to vector-producing cells of human origin. we reasoned that sindbis-virus-based vectors might be ideal for galv.fus gene transfer because high-titer stocks ...200415368589
using sindbis viral vectors for specific detection and suppression of advanced ovarian cancer in animal models.we studied the therapeutic value of sindbis vectors for advanced metastatic ovarian cancer by using two highly reproducible and clinically accurate mouse models: a scid xenograft model, established by i.p. inoculation of human es-2 ovarian cancer cells, and a syngenic c57bl/6 model, established by i.p. inoculation of mouse mosec ovarian cancer cells. we demonstrate through imaging, histologic, and molecular data that sindbis vectors systemically and specifically infect/detect and kill metastasiz ...200415374985
antigenic and genetic typing of whataroa viruses in australia.we recently characterized three novel alphaviruses isolated from mosquitoes captured in new south wales, australia. initial cross-neutralization studies revealed antigenic similarity to the sindbis virus (sinv)-like whataroa virus (whav), heretofore found only in new zealand. nucleotide sequence analysis showed that the whav-like viruses shared >99% nucleotide sequence similarity with each other, and 96-97% similarity with prototype whav. enzyme-linked immunosorbent assay reactions of a panel of ...200415381803
mannose-specific plant lectins from the amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection.the plant lectins derived from galanthus nivalis (snowdrop) (gna) and hippeastrum hybrid (amaryllis) (hha) selectively inhibited a wide variety of human immunodeficiency virus type 1 (hiv-1) and hiv-2 strains and clinical (cxcr4- and ccr5-using) isolates in different cell types. they also efficiently inhibited infection of t lymphocytes by a variety of mutant virus strains. gna and hha markedly prevented syncytium formation between persistently infected hut-78/hiv cells and uninfected t lymphocy ...200415388446
sindbis virus--an effective targeted cancer therapeutic.viral therapies for cancer therapy have many potential positive attributes. these include the ability to specifically infect targeted cells, specifically express toxic or immune-enhancing genes, and the ability to specifically replicate within a tumor cell. despite these biological advantages, efficacy to date has been limited. a recent report demonstrates that the sindbis virus has remarkable properties in three challenging areas of gene therapy - specificity, efficacy and delivery, suggesting ...200415450742
targeted in vivo expression of proteins in the calyx of held.the calyx of held serves as a model for synaptic transmission in the mammalian central nervous system. while offering unique access to the biophysics of presynaptic function, studies addressing the molecular mechanisms of neurotransmitter exocytosis in this model have been mainly limited to pharmacological interventions. to overcome this experimental limitation we used stereotaxic delivery of viral gene shuttles to rapidly and selectively manipulate protein composition in the calyx terminal in v ...200415452710
abstracts of the fourth international symposium on molecular insect science. may 28-june 2, 2002. tucson, arizona, usa. 200215455051
characterization of an endogenous gene expressed in aedes aegypti using an orally infectious recombinant sindbis virus.sindbis virus expression vectors have been used successfully to express and silence genes of interest in vivo in several mosquito species, including aedes aegypti, ae. albopictus, ae. triseriatus,culex pipiens, armigeres subalbatus and anopheles gambiae. here we describe the expression of an endogenous gene, defensin, in ae. aegypti using the orally infectious sindbis virus, mre/3'2j expression vector. we optimized conditions to infect mosquito larvae per os using c6/36ae. albopictus cells infec ...200115455070
alphavirus expression systems: applications to mosquito vector studies.in this review, steve higgs, ann powers and ken olson describe how alphavirus expression systems, based on infectious cdna clones of sindbis virus, constitute a novel rna virus delivery system suitable for the efficient expression of heterologous gene products or rna sequences in mosquito cells or adult mosquitoes. the technique permits ready assessment of molecular genetic-based methods of intracellular interference to infection and provides a powerful new tool for molecular biological studies ...199315463689
trans-packaged west nile virus-like particles: infectious properties in vitro and in infected mosquito vectors.a trans-packaging system for west nile virus (wnv) subgenomic replicon rnas (reprnas), deleted for the structural coding region, was developed. wnv reprnas were efficiently encapsidated by the wnv c/prm/e structural proteins expressed in trans from replication-competent, noncytopathic sindbis virus-derived rnas. infectious virus-like particles (vlps) were produced in titers of up to 10(9) infectious units/ml. wnv vlps established a single round of infection in a variety of different cell lines w ...200415479801
evolutionary transition toward defective rnas that are infectious by complementation.passage of foot-and-mouth disease virus (fmdv) in cell culture resulted in the generation of defective rnas that were infectious by complementation. deletions (of nucleotides 417, 999, and 1017) mapped in the l proteinase and capsid protein-coding regions. cell killing followed two-hit kinetics, defective genomes were encapsidated into separate viral particles, and individual viral plaques contained defective genomes with no detectable standard fmdv rna. infection in the absence of standard fmdv ...200415479809
cd209l (l-sign) is a receptor for severe acute respiratory syndrome coronavirus.angiotensin-converting enzyme 2 (ace2) is a receptor for sars-cov, the novel coronavirus that causes severe acute respiratory syndrome [li, w. moore, m. j., vasilieva, n., sui, j., wong, s. k., berne, m. a., somasundaran, m., sullivan, j. l., luzuriaga, k., greenough, t. c., et al. (2003) nature 426, 450-454]. we have identified a different human cellular glycoprotein that can serve as an alternative receptor for sars-cov. a human lung cdna library in vesicular stomatitis virus g pseudotyped ret ...200415496474
rna encoding the mpt83 antigen induces protective immune responses against mycobacterium tuberculosis infection.we have previously demonstrated that vaccination of mice with plasmid dna vectors expressing immunodominant mycobacterial genes induced cellular immune responses and significant protection against challenge with mycobacterium tuberculosis. we demonstrate here, using in vitro-synthesized rna, that vaccination with dna or rna constructs expressing the m. tuberculosis mpt83 antigen are capable of inducing specific humoral and t-cell immune responses and confer modest but significant protection agai ...200415501761
expression of antiapoptotic genes bcl-xl and ced-9 in tomato enhances tolerance to viral-induced necrosis and abiotic stress.d satellite rna (satrna) is a strain of cucumber mosaic virus (cmv) satrna that induces an epidemic lethal disease in tomato. no natural resistance or tolerance has ever been found. previously, we demonstrated the involvement of programmed cell death in disease development. here, transgenic tomato plants expressing animal antiapoptotic genes bcl-xl and ced-9 were generated through agrobacterium-mediated transformation. high expression of bcl-xl or ced-9 affected plant growth and seed development ...200415505199
analysis of adaptive mutations in kunjin virus replicon rna reveals a novel role for the flavivirus nonstructural protein ns2a in inhibition of beta interferon promoter-driven transcription.the establishment of persistent noncytopathic replication by replicon rnas of a number of positive-strand rna viruses usually leads to generation of adaptive mutations in nonstructural genes. some of these adaptive mutations (e.g., in hepatitis c virus) increase the ability of rna replication to resist the antiviral action of alpha/beta interferon (ifn-alpha/beta); others (e.g., in sindbis virus) may also lead to more efficient ifn production. using puromycin-selectable kunjin virus (kun) replic ...200415507609
serotype-specific entry of dengue virus into liver cells: identification of the 37-kilodalton/67-kilodalton high-affinity laminin receptor as a dengue virus serotype 1 receptor.dengue virus, the causative agent of dengue fever, dengue shock syndrome, and dengue hemorrhagic fever, infects susceptible cells by initially binding to a receptor(s) located on the host cell surface. evidence to date suggests that receptor usage may be cell and serotype specific, and this study sought to identify dengue virus serotype 1 binding proteins on the surface of liver cells, a known target organ. by using a virus overlay protein binding assay (vopba), in both nondenaturing and denatur ...200415507651
the nucleoprotein is required for efficient coronavirus genome replication.the construction of a set of transmissible gastroenteritis coronavirus (tgev)-derived replicons as bacterial artificial chromosomes is reported. these replicons were generated by sequential deletion of nonessential genes for virus replication, using a modified tgev full-length cdna clone containing unique restriction sites between each pair of consecutive genes. efficient activity of tgev replicons was associated with the presence of the nucleoprotein provided either in cis or in trans. tgev rep ...200415507657
ebna2 is required for protection of latently epstein-barr virus-infected b cells against specific apoptotic stimuli.in addition to functioning as a transcriptional transactivator, epstein-barr virus ebna2 interacts with nur77 to protect against nur77-mediated apoptosis. estrogen-regulated ebna2 in ereb2-5 cells was replaced by either ebna2 or ebna2 with a deletion of conserved region 4 (ebna2deltacr4). both ebna2-converted and ebna2deltacr4-converted ereb2-5 cells grew in the absence of estrogen and expressed lmp1. treatment with tumor necrosis factor alpha did not induce apoptosis of ebna2- or ebna2deltacr4- ...200415507659
cross talk between metabotropic and ionotropic glutamate receptor-mediated signaling in parallel fiber-induced inositol 1,4,5-trisphosphate production in cerebellar purkinje cells.in many excitatory glutamatergic synapses, both ionotropic glutamate receptors (iglurs) and metabotropic glutamate receptors (mglurs) are closely distributed on the postsynaptic membrane. however, the functional significance of the close distribution of the two types of glutamate receptors has not been fully clarified. in this study, we examined the functional interaction between iglur and mglur at parallel fiber (pf)--> purkinje cell synapses in the generation of inositol 1,4,5-trisphosphate (i ...200415509738
retinoid x receptor regulates nur77/tr3-dependent apoptosis [corrected] by modulating its nuclear export and mitochondrial targeting.retinoid x receptor (rxr) plays a central role in the regulation of intracellular receptor signaling pathways by acting as a ubiquitous heterodimerization partner of many nuclear receptors, including the orphan receptor nur77 (also known as tr3 [corrected] or ngfi-b), which translocates from the nucleus to mitochondria, where it interacts with bcl-2 to induce apoptosis. here, we report that rxralpha is required for nuclear export and mitochondrial targeting of nur77 through their unique heterodi ...200415509776
[antibodies against mosquito-born viruses in human population of an area of central bohemia affected by the flood of 2002].in the central-bohemian area affected by the flood of 2002, 497 residents were screened for antibodies against the mosquito-borne viruses tahyna (tahv), west nile (wnv), sindbis (sinv) and batai (batv; syn. calovo) using the haemagglutination-inhibition (hit) and plaque-reduction neutralization (prnt) tests. blood samples were collected in september 2002 when the mosquito populations showed the maximum density following the flood. antibodies against tahv (16.5% persons in prnt, 14.9% in hit), si ...200415524269
preferential targeting of vesicular stomatitis virus to breast cancer cells.vesicular stomatitis virus (vsv) is a candidate for development for cancer therapy. we created a recombinant replicating vsv (rrvsv) with an altered surface protein that targeted preferentially to breast cancer cells. the rrvsv genome contained a single glycoprotein (gp) gene derived from sindbis virus. this gene expressed a chimeric sindbis e2 binding gp and the native sindbis e1 fusion gp. the chimeric e2 binding gp, called sindbis-sca-erbb2, was modified to reduce its native binding function ...200415527831
role of isg15 protease ubp43 (usp18) in innate immunity to viral infection.innate immune responses provide the host with an early protection barrier against infectious agents, including viruses, and help shape the nature and quality of the subsequent adaptive immune responses of the host. expression of isg15 (ucrp), a ubiquitin-like protein, and protein isgylation are highly increased upon viral infection. we have identified ubp43 (usp18) as an isg15 deconjugating protease. protein isgylation is enhanced in cells deficient in ubp43 (ref. 6). here we have examined the r ...200415531891
alphaviral cytotoxicity and its implication in vector development.a great variety of viruses have been engineered to serve as expression vectors. among them, the alphaviruses semliki forest virus and sindbis virus represent promising tools for heterologous gene expression in a wide variety of host cells. several applications have already been described in neurobiological studies, in gene therapy, for vaccine development and in cancer therapy. both viruses trigger stress pathways in the cells they infect, sometimes culminating in the death of the host. this inh ...200515542620
the zinc finger antiviral protein directly binds to specific viral mrnas through the ccch zinc finger motifs.the zinc finger antiviral protein (zap) is a recently isolated host antiviral factor. it specifically inhibits the replication of moloney murine leukemia virus (mlv) and sindbis virus (sin) by preventing the accumulation of viral rna in the cytoplasm. for this report, we mapped the viral sequences that are sensitive to zap inhibition. the viral sequences were cloned into a luciferase reporter and analyzed for the ability to mediate zap-dependent destabilization of the reporter. the sensitive seq ...200415542630
coexpression of hepatitis c virus e1 and e2 chimeric envelope glycoproteins displays separable ligand sensitivity and increases pseudotype infectious titer.we have previously reported that a pseudotype virus generated by reconstitution of hepatitis c virus (hcv) chimeric envelope glycoprotein e1-g or e2-g on the surface of a temperature-sensitive mutant of vesicular stomatitis virus (vsvts045) interacts independently with mammalian cells to initiate infection. here, we examined whether coexpression of both of the envelope glycoproteins on pseudotype particles would augment virus infectivity and/or alter the functional properties of the individual s ...200415542636
proteomics computational analyses suggest that the carboxyl terminal glycoproteins of bunyaviruses are class ii viral fusion protein (beta-penetrenes).the bunyaviridae family of enveloped rna viruses includes five genuses, orthobunyaviruses, hantaviruses, phleboviruses, nairoviruses and tospoviruses. it has not been determined which bunyavirus protein mediates virion:cell membrane fusion. class ii viral fusion proteins (beta-penetrenes), encoded by members of the alphaviridae and flaviviridae, are comprised of three antiparallel beta sheet domains with an internal fusion peptide located at the end of domain ii. proteomics computational analyse ...200415544707
sindbis viruses and other alphaviruses as cause of human arthritic disease.amongst the arthritis-causing arboviruses, i.e. those spread by insects, the alphavirus group is of special interest. these viruses occasionally cause vast outbreaks, such as o'nyong-nyong in africa in 1959. in fennoscandia, sindbis-related ockelbo, pogosta, or karelian fever viruses have been found to cause significant morbidity. the major symptoms in addition to joint inflammation are fever, fatigue, headache and rash. the joint symptoms may persist for weeks, even months. the diagnosis is bas ...200415554947
two amino acid mutations in the capsid protein of type 2 porcine circovirus (pcv2) enhanced pcv2 replication in vitro and attenuated the virus in vivo.porcine circovirus type 2 (pcv2) is the primary causative agent of postweaning multisystemic wasting syndrome (pmws) in pigs. to identify potential genetic determinants for virulence and replication, we serially passaged a pcv2 isolate 120 times in pk-15 cells. the viruses harvested at virus passages 1 (vp1) and 120 (vp120) were biologically, genetically, and experimentally characterized. the pcv2 vp120 virus replicated in pk-15 cells to a titer similar to that of the pk-15 cell line-derived non ...200415564454
a conserved histidine in the ij loop of the semliki forest virus e1 protein plays an important role in membrane fusion.the enveloped alphavirus semliki forest virus (sfv) infects cells via a low ph-triggered membrane fusion reaction mediated by the e1 protein. e1 is a class ii fusion protein that contains the hydrophobic fusion peptide loop and converts to a stable homotrimer during the fusion reaction. intriguingly, the fusion loop is closely associated with a loop connecting the i and j beta-strands. this ij loop plays a role in the cholesterol dependence of membrane fusion and is specifically susceptible to p ...200415564465
protein kinase c-alpha activity is required for respiratory syncytial virus fusion to human bronchial epithelial cells.respiratory syncytial virus (rsv) infection activates protein kinase c (pkc), but the precise pkc isoform(s) involved and its role(s) remain to be elucidated. on the basis of the activation kinetics of different signaling pathways and the effect of various pkc inhibitors, it was reasoned that pkc activation is important in the early stages of rsv infection, especially rsv fusion and/or replication. herein, the role of pkc-alpha during the early stages of rsv infection in normal human bronchial e ...200415564481
regulation of hcn channel surface expression by a novel c-terminal protein-protein interaction.hyperpolarization-activated cation currents (i(h)) are carried by channels encoded by a family of four genes (hcn1-4) that are differentially expressed within the brain in specific cellular and subcellular compartments. hcn1 shows a high level of expression in apical dendrites of cortical pyramidal neurons and in presynaptic terminals of cerebellar basket cells, structures with a high density of i(h). expression of i(h) is also regulated by neuronal activity. to isolate proteins that may control ...200415564593
alphaviruses and their derived vectors as anti-tumor agents.the alphaviruses semliki forest virus (sfv) and sindbis virus have recently been developed as prototype anti-cancer agents. these are rna-containing enveloped viruses that code for only 9 proteins of unique sequence. the standard recombinant sfv vector system consists of suicide particles containing recombinant rna. in addition, alphavirus vectors capable of limited multiplication in the host are also being developed. several strategies are being adopted to construct prototype sfv vectors for ca ...200415578917
rna interference acts as a natural antiviral response to o'nyong-nyong virus (alphavirus; togaviridae) infection of anopheles gambiae.rna interference (rnai) is triggered in eukaryotic organisms by double-stranded rna (dsrna), and it destroys any mrna that has sequence identity with the dsrna trigger. the rnai pathway in anopheles gambiae can be silenced by transfecting cells with dsrna derived from exon sequence of the a. gambiae argonaute2 (agago2) gene. we hypothesized that rnai may also act as an antagonist to alphavirus replication in a. gambiae because rna viruses form dsrna during replication. silencing agago2 expressio ...200415583140
ethnomedicinal uses of momordicacharantia (cucurbitaceae) in togo and relation to its phytochemistry and biological activity.investigation of the traditional uses of momordica charantia (cucurbitaceae) in togo (west africa) showed that it is one of the most important local medicinal plants both for ritual and ethnomedical practices. there was a high degree of consensus (>50%) for use in the treatment of gastrointestinal and viral disease among 47 groups of village informants in the general population, while 19 traditional healers reported a larger and broader set of uses. the use by informants in gaur and kwa language ...200515588650
expression of cellular oncogene bcl-xl prevents coronavirus-induced cell death and converts acute infection to persistent infection in progenitor rat oligodendrocytes.murine coronavirus mouse hepatitis virus (mhv) causes persistent infection of the central nervous system (cns) in rodents, which has been associated with demyelination. however, the precise mechanism of mhv persistence in the cns remains elusive. here we show that the progenitor oligodendrocytes (central glial 4 [cg-4] cells) derived from newborn rat brain were permissive to mhv infection, which resulted in cell death, although viral replication was restricted. interestingly, treatment with feta ...200515596800
prevention of virus persistence and protection against immunopathology after borna disease virus infection of the brain by a novel orf virus recombinant.the parapoxvirus orf virus represents a promising candidate for novel vector vaccines due to its immune modulating properties even in nonpermissive hosts such as mouse or rat. the highly attenuated orf virus strain d1701 was used to generate a recombinant virus (d1701-vrvp40) expressing nucleoprotein p40 of borna disease virus, which represents a major antigen for the induction of a borna disease virus-specific humoral and cellular immune response. infection with borna disease virus leads to dis ...200515596826
sindbis virus with a tricomponent genome.we established a system for propagation of sindbis virus (sin)-based replicons in tissue culture in the form of a tricomponent genome virus. three rna fragments containing complementing genetic information required for virus replication are packaged into separate viral particles, and each cell produces at least 1,000 packaged replicons and the number of packaged helpers sufficient to perform the next passage. this system can be used to generate large stocks of packaged replicons. the formation o ...200515596860
rapid functional cloning of cell adhesion molecules. 200415597539
the use of a double subgenomic sindbis virus expression system to study mosquito gene function: effects of antisense nucleotide number and duration of viral infection on gene silencing efficiency.recently we established a simple, effective antisense strategy using a double subgenomic sindbis (dssin) virus expression system to study gene function in mosquitoes. in this study, we further elucidate the effects of antisense nucleotide number and duration of viral infection on mosquito gene silencing efficiency by the dssin virus expression system. over 15 days post virus infection, the degree of parasite melanization was progressively reduced by more than 95%, 75% and 55% in the mosquito arm ...200415606808
efficient functional pseudotyping of oncoretroviral and lentiviral vectors by venezuelan equine encephalitis virus envelope proteins.murine oncoretroviruses and lentiviruses pseudotyped with envelope proteins of alphaviruses have shown great potential in providing broad-host-range, stable vectors for gene therapy. unlike vesicular stomatitis virus g protein-pseudotyped vectors, they are not neutralized by complement and do not appear to cause significant tissue damage. here we report the production of murine oncoretroviral and lentiviral vectors pseudotyped with the envelope proteins of venezuelan equine encephalitis virus (v ...200515613303
efficient rescue of hepatitis c virus rna replication by trans-complementation with nonstructural protein 5a.studies of hepatitis c virus (hcv) rna replication have become possible with the development of subgenomic replicons. this system allows the functional analysis of the essential components of the viral replication complex, which so far are poorly defined. in the present study we wanted to investigate whether lethal mutations in hcv nonstructural genes can be rescued by trans-complementation. therefore, a series of replicon rnas carrying mutations in ns3, ns4b, ns5a, and ns5b that abolish replica ...200515613318
glycine-amide is an active metabolite of the antiretroviral tripeptide glycyl-prolyl-glycine-amide.the chemically modified tripeptide glycyl-prolyl-glycine-amide (gpg-nh(2)) inhibits replication of human immunodeficiency virus (hiv) type 1 (hiv-1) in vitro, probably by interfering with capsid formation. the aim of the present study was to determine whether the metabolites glycyl-proline (gp-oh), glycine (g-oh), prolyl-glycine-amide (pg-nh(2)), proline (p-oh), and glycine-amide (g-nh(2)) from proteolytic cleavage may inhibit the replication of hiv-1 in vitro. pg-nh(2) has previously been shown ...200515616273
bioinformatic mapping of alkb homology domains in viruses.alkb-like proteins are members of the 2-oxoglutarate- and fe(ii)-dependent oxygenase superfamily. in escherichia coli the protein protects rna and dna against damage from methylating agents. 1-methyladenine and 3-methylcytosine are repaired by oxidative demethylation and direct reversal of the methylated base back to its unmethylated form. genes for alkb homologues are widespread in nature, and eukaryotes often have several genes coding for alkb-like proteins. similar domains have also been obse ...200515627404
construction and applications of yellow fever virus replicons.subgenomic replicons of yellow fever virus (yfv) were constructed to allow expression of heterologous reporter genes in a replication-dependent manner. expression of the antibiotic resistance gene neomycin phosphotransferase ii (neo) from one of these yfv replicons allowed selection of a stable population of cells (bhk-rep cells) in which the yfv replicon persistently replicated. bhk-rep cells were successfully used to trans-complement replication-defective yfv replicons harboring large internal ...200515629769
il-15-independent antiviral function of primary and memory cd8+ t cells.memory cd8+ t cells are comprised of cd122hi il-15-dependent and cd122lo il-15-independent subsets. induction and retention of il-15-independent memory cd8+ t cells was assessed in il-15-/- and wild-type (wt) mice immunized with recombinant vaccinia virus (rvv) or sindbis virus (rsin) vectors expressing the identical foreign epitope. both vectors induced epitope-specific cd8+ t cell expansion and function, independent of il-15. similar kinetics of rvv clearance confirmed effective cd8+ t cell fu ...200515629776
early events in the pathogenesis of eastern equine encephalitis virus in mice.to elucidate the pathogenesis of eastern equine encephalitis (eee) virus infections, we used histopathology, immunohistochemistry, and in situ hybridization to track the spread and early cellular targets of viral infection in mice. young mice were inoculated with virulent eee virus in their right rear footpad and were followed in a time-course study for 4 days. virulent eee virus produced a biphasic illness characterized by an early self-limiting replication phase in peripheral tissues followed ...200515632009
alphavirus replicon particles containing the gene for her2/neu inhibit breast cancer growth and tumorigenesis.overexpression of the her2/neu gene in breast cancer is associated with an increased incidence of metastatic disease and with a poor prognosis. although passive immunotherapy with the humanized monoclonal antibody trastuzumab (herceptin) has shown some effect, a vaccine capable of inducing t-cell and humoral immunity could be more effective.200415642163
protective effects of task-3 (kcnk9) and related 2p k channels during cellular stress.tandem pore domain (or 2p) k channels form a recently isolated family of channels that are responsible for background k currents in excitable tissues. previous studies have indicated that 2p k channel activity produces membrane hyperpolarization, which may offer protection from cellular insults. to study the effect of these channels in neuroprotection, we overexpressed ph-sensitive 2p k channels by transfecting the partially transformed c8 cell line with these channels. tandem pore weak inward r ...200515649441
west nile virus inhibits the signal transduction pathway of alpha interferon.west nile virus (wnv) is a human pathogen that can cause neurological disorders, including meningoencephalitis. experiments with mice and mammalian cell cultures revealed that wnv exhibited resistance to the innate immune program induced by alpha interferon (ifn-alpha). we have investigated the nature of this inhibition and have found that wnv replication inhibited the activation of many known ifn-inducible genes, because it prevented the phosphorylation and activation of the janus kinases jak1 ...200515650160
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